The overall goal of this proposal is to identify how perinatal methylmercury or inorganic mercury exposure affects growth and development of the central and peripheral nervous systems of the rat, with emphasis on the biochemical factors which regulate maturation and function of synapses. Systems to be studied include noradrenergic, dopaminergic and serotonergic neurons in the brain, noradrenergic pathways in heart and cholinergic innervation of the adrenal medulla. These studies will concentrate on normal and mercury-perturbed development of presynaptic and postsynaptic elements and synaptic function by procedures which will determine the time course of synaptogenesis (synaptic uptake mechanisms), maturation of synaptic storage vesicles and the functional state of postsynaptic response systems (receptors and receptor mediated stimulation of: ornithine decarboxylase, phospholipid synthesis or secretory responses). The different model tissues will be used to determine how mercury-induced perturbations of presynaptic and/or postsynaptic elements combine to affect overall synaptic function and hence to cause subtle alterations in behavior or performance. Related studies will be conducted to elucidate the underlying mechanisms by which perinatal mercury exposure affects neuronal development, including: maternal nutritional, hormonal and/or behavioral factors; the role of perturbations in general cellular growth; exposure thresholds and critical developmental periods for teratologic effects of mercury. By identifying specific sites and types of alterations, these studies may enable a rational therapeutic approach to prevention or amelioration of the functional neuronal alterations produced by perinatal mercury exposure after exposure has taken place. Additionally, by determining the specific critical periods in perinatal development in which mercury alters neuron ontogeny, this will enable identification of those stages at which the immature nervous system is at the greatest risk.